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Year 5 MEDICINE Pathology > Hematology > Flashcards

Hematology Flashcards

1
Q

Virchows triad for thrombosis?

A

blood

vessel wall - antithrombotic normally, secretes anticoagulants and antiplatelet factors. inflammation and injury makes it Prothrombotic

blood flow - stasis:
Immobility = Surgery, Paraparesis Travel
Compression = Tumour, pregnancy
Viscosity = Polycythaemia, Paraprotein
Congenital vascular abnormalities

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2
Q

state immediate anticoagulant therapies and their mechanisms
Eg heparin mechanism and how to reverse

A

heparin - potentiates antithrombin. reverse with protamine

direct Xa inhibitors and IIa inhibitors

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3
Q

acute leukemia features?

A

rapid onset
blast cells (immature cells) - high nucleus:cytoplasm ratio
bone marrow failure ->anemia, neutropenia (infections), thrombocytopenia (bleeding)

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4
Q

mutation in chronic myeloid leukemia occurs at which level?

A

pluripotent hematopoeitic stem cells

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5
Q

Acute myeloid leukemia AML
stats?
pathology?

A

increases with age
40% in adults
many have abberations in chromosome count or structure eg t(8,21) -> RUNX1/RUNX1T1 fusion
t(15,17) -> acute promyelocytic lueukemia!!
inv(16) -> may see eosinophilia

two hits
type 1 - promote proliferation and survival
type 2 - block differentiation

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6
Q

t(15,17) translocation occurs in?
Clinical effect?

most important diagnostic test?

A

acute promyelocytic leukemia - must be treated quickly.
can cause massive hemorrhage eg cerebral hemorrhage
accumulation of promyelocytes NOT blast cells
causes DIC!
hypergranular, multiple auer rods!!!
may habve bilobed nuclei (variant apl)

cytogenetic analysis/molecular/fish -> looking for translocation

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7
Q

what chromosomal duplications are common in AML?

A

+8
+21 (downs)

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8
Q

in a patient with AML with normal chromosomes, what molecular abnormality could have occured?

A

point mutation NPM1, CEBPA
partial duplication FLT3
loss of tumour suppressor genes

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9
Q

AML vs ALL?

Which is Mpo +ve?
What are the different cell markers expressed by these?

A

AML has fine granules in cytoplasm - you probably cant see them. has aueur rods (pathoneumonic of myeloid neoplasm)

cytochemical staining:
Myeloperoxidase -> stains for Myeloid cells (tell from name) -> brown stain
sudan black stain -> +ve myeloid cells
non-specific esterase -> +ve myeloid cells

Immunophenotyping -> identify cell type based surface or cytoplasmic antigen only expressed on lymphoid vs myeloid cells. xamples include

- immunocytochemistry/immunohistochemistry = using antibodies + florescent enzyme
- flow cytometry - will tell you markers eg CD13!! AND CD33!! expressed by myeloid cells -> AML
(ALL is Tdt +ve -> T cells express CD3!, B cells CD19!, CD10!)

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10
Q

AML features?

A

bone marrow failure ->anemia, neutropenia (infections - can be as serious as septic shock), thrombocytopenia (bleeding)

inflitration of tissues by leukemic cells -> spleenomegaly, hepatomegaly, gum infiltration if monocytic, lymphadenopathy occasionally

Skin/CNS disease eg cranial nerve palsy

DIC -> vascular obstruction, gangrene

hyper viscosity of wbc = retinal hemorrhage

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11
Q

AML diagnosis

A

blood film!
- blasts and auer rods
- if no auer rods, immunophotyping to distinguish AML from ALL
- if aleukemic lukemia suspected = bone marrow aspirate

once diagnosed, do cytogenetic studies to guide treatment

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12
Q

AML treatment

A

Red cells, platelets, FFP/Cryoprecipitate if DIC, antibiotics if infection, allopurinol if uric acid release from chemo

combination chemo

all trans retinoic acid for acute promyelocytic leukemia

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13
Q

ALL stats?
features?
diagnosis?

A

occurs in children
most common childhood malignancy!. AML rare in child

bone marrow failure: anemia (pallor), neutropenia, thrombocytopenia (bruising)

local infiltration: lymphadenopathy (more prominent than AML), thymic inflitration (mediastinal mass!! - this does not occur in AML) if T lineage may occur, spleenomegaly, hepatomegaly

bone pain!

CNS, testes, kidneys

blood film
immunophenotype - important as T-ALL and B-ALL are treated differently. best technique to diagnose

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14
Q

where does ALL start?

which patients have better prognosis?


treatment

A

B-ALL in bone marrow
T-ALL can start in thymus -> thymic enlargement -> mediastinal mass

patients with hyperdiploidy eg t(12,21) t(1,19)

patients with t(9,22) due to tyrosine kinase inhibitors/ imatinib that inhibit BCR-ABL-> which is philadelphia cchromosome also seen in CML

chemo
CNS directed therapy as lymphoblasts can enter CSF
supportive care: blood products, antibiotics

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15
Q

how are childrens FBCs different from adults?

how are newborn babies different from adults?

how is sthe experience of illness different for kids?

A

children have higher lymphocyte counts and MCVs
have LOWER hemoglobin concs

newborns have higher lymphoctytes and MCVs
HIGHER hemoglobin conc

kids more likely to respond with lymphocytosis
disease or treatment can cause delayed puberty and growth retardation may happen in kids

neonate reference range for FBC different from a child and adult

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16
Q

causes of anemia in fetus

A

parvovirus infection in mother
shared twin placenta
fetal to maternal transmission

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17
Q

causes of polycythemia in fetus or neonate

A

placental insufficiency
itrauterine hypoxia
twin to twin transfusion

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18
Q

Why does sickle cell anemia not manifest at birth?

A

it is a Beta chain defect not alpha chain
clinical features manifest as hemoglobin F synthesis decreases and BetaS and hemoglobin S production increase

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19
Q

why is sickle cell anemia different in child vs adult?
What conditions occur only in child?

A

in child, red marrow extends throughout skeleton and is susceptible to infarction

in adult, it is confined to axial skeleton

thus hand-foot syndrome only seen in children, typically in fist 2 years

infant still has a functioning spleen so splenic sequestration can occur -> severe anemia, shock

in adults, spleen undergoes multiple infarctions and thus no longer succeptible to splenic sequestration but hypospleenism can occur

red cell aplasia more common in children due to highr liklihood of coming across parvovirus as a child

stroke more common in children - smaller cerebral arteries

seen in children:
- hand foot syndrome
- splenic sequestration

-

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20
Q

sickle cell anemia management in child?

A

vaccinate
educate important to give penicillin and folic acid to children

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21
Q

if siblings with sickle cell anemia present simultaneously with severe anaemia and low reticulocyte count, what is the likely diagnosis?

A

Parvovirus B19

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22
Q

how does blood film in sickle cell anemia and sickle cell trait differ?

A

sickle cells wont be seen in blood film for sickle cell trait

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23
Q

what is beta thalasemia?

how does heterozygous and homozygous present?

A

reduced synthesis of Beta globin chain and therefore hemoglobin A

heterozygous = harmless
homozygous = severe anemia, fatal without blood transfusion in first few years

homozygous
anemia -> heart failure, growth retardation
erothropoeitic drive -> bone expansion, hepatomegaly, spleenomegaly (extramedullary hematopoeisis)
iron overload -> heart failure, gonadal failure

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24
Q

beta thalesemmia major treatment?

A

blood transfusion to maintain Hb
Will cause iron overload -> desfeiroxamine for chelation

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25
Q

causes of hemolytic anemia in child?

A

inherited
acquired
- hemolytic disease of newborn (ABO or Rh antibodies)
- defects in red cell membrane (hereditary spherocytosis and elliptocytosis), red cell enzymes (glycolytic pathway, pentose shunt/G6PD which mainly affects males), hemoglobin molecule

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26
Q

how to diagnose hemolytic anemia?

A

anemia
signs of red blood cell breakdown - jaundice, spleenomegaly, increased unconjugated bilirubin
increased reticulocyte count? bone expansion?
abnormal red cells in blood film?

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27
Q

how can hemophila A and B present

differential diagnoses?

investigations?

A

bleeding following circumcision
hemarthroses when starting to walk
bruises
post traumatic bleeding

differentials: inherited thrombocytopenia or platelet function defect, acquired defects eg acute leukemia, itp, non accidental injury, henoch schonlein purpura

blood film
platelet count
coagulation screen
assay of relevant factors

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28
Q

questions to ask to rule out inherited defects of coagulation

managment?

A

umbilical cord bleeding after cut?
bleeding with heel prick test?
hematomas after vitamin k injection or vaccinations?
bleeding after circumcision?

family history

treating of bleeding
prophylactic anticoagulants

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29
Q

VWD presentation?
investigation?
differential diagnosis?
treatment?

A

mucosal bleeding - affects platelet FUNCTION, not count
bruises
post trauma bleeding

coagulation screen - elongated aPTT
factor 8 assay
FH history
bleeding time

differential diagnosis is hemophila A as factor 8 level is reduced in both diseases

lower purity factor 8 concentrate

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30
Q

1 year old with joint bleeding, HB WBC and platelet count normal. aPTT prolonged, normal PT, bleeding time normal.

what is the diagnosis?

A

hemophilia A most likely

(because 5x more common than hemophila B_

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31
Q

ITP presentation?
diagnosis?

A

petechiae
bruises
blood blisters in mouth

history - febrile illness
drugs
blood count film - confirm thrombocytopenia
bone marrow aspirate - not usually needed

treatment is observation
corticosteroids if serious hemorrhage or blisters in mouth
high dose intravenous immunoglobulin
intravenous anti Rh D if RH positive

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32
Q

what factor is involved in formation of stable platelet plug?

A

VWF

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33
Q

describe 2 ways in which platelet adhesion to endothelium occurs

A

directly through glycoprotein 1A
through glycoprotein 1B with assistance of VWF

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34
Q

describe how platelet aggregation occurs

A

after adhesion, release of ADP and thromboxane

which promote aggregation via glycoprotein 2B 3A (which allows fibrinogen to bind/fibrinogen receptor)

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35
Q

thromboxane A2 role?
prostacyclin PGI2 role?

A

- induces platelet aggregation
- inhibits platelet aggregation

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36
Q

thrombin function?

A

cleaves fibrinogen to fibrin!! (stable clot)
activates platelets
activates clotting factors

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37
Q

mechanism of blood clot removal? Describe natural body process

A

plasminogen is converted to plasmin by tpa
plasmin cleaves fibrin

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38
Q

how is thrombin inhibited?
effect of heparin?

A

antithrombin 3 binds it
auguments effect of antithrombin

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39
Q

protein C and protein S function?





How does Factor V leiden present?

A

when activated, they are antithrombotic as they degrade factor V and Factor 8

thrombomodulin binds protein C activates it, APC binds protein S to cleave factor V and 8

mutation in factor 5 making it resistant to breakdown by APC -> thrombosis

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40
Q

causes of APC resistance?

A

factor 5 leiden
high levels of factor 8

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41
Q

state 2 genetic causes of bleeding disorders

state 2 acquired causes

A

1. platelet abnormalities
2. clotting factor deficiencies eg hemophilia
3. vascular/endothelium - scurvy

1. liver disease (site of clotting factor synthesis)
2. vitamin K deficiency
3. autoimmune destruction of platelets

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42
Q

most common cause of thrombocytopenia?

A

immune mediated is most common cause
- idiopathic most common
- drugs
- connective tissue disease
- lymphoproliferative disease eg leukemia
- sarcoidosis


non immune:
- DIC
- Microangiopathic hemolytic anemia

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43
Q

ITP managment?

A

platelet count between 20 -50,000 - you only treat if bleeding -> steroids, IVIG

count less than 20,000 -> whether bleeding or not -> you treat as above and hospitalise

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44
Q

describe two causes of thrombocytopenia recognized through blood film

A

B12 deficiency - Large rbc/macrocytosis

AML - myeolid blasts

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45
Q

hemophilia symptoms

A

hemarthrosis - fixed joints
soft tissue hematomas: muscle atrophy, shortened tendons
bleeding in urinary tracts, CNS, neck

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46
Q

causes of Vitamin K deficiency?

A

malabsorption
malnutrition
biliary obstruction
antibiotics

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47
Q

common causes of DIC

A

sepsis - eg meningitis
trauma
malignancy
toxins - eg snake venom

blood film - spliced rbcs

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48
Q

most common cause of intravascular hemolytic anemia?

A

malaria

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49
Q

signs of hemolytic anemia?

A

anemia
increased reticulocyte
increased folate requirement
susceptibility to parvovirus B19 - aplastic crisis, low or absent reticulocyte count - only early forms of RBC seen in marrow as differentiation arrested
gallstones -> risk increases with co existence of Gilberts Syndrome
iron overload -> seen on liver biopsy


clinical
- pallor
- jaundice
- spleenomegaly
- pigmenturia eg in hemoglobinuria
- Family history

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50
Q

biochemical findings in intravascular hemolysis?

A

increased LDH
decreased haptoglobins

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51
Q

hereditary spherocytosis

blood film findings?


test?

A

ankyrin
Beta spectrin

smaller cells, lack central pallor, MCHC increased

osmotic fragility
dye binding test

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52
Q

hereditary elliptocytosis

blood film findings?

A

alpha spectrin
beta spectrin

elliptical cells

hereditary pyropoikilocytosis = homozygous form = severe anemia

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53
Q

G6PD deficiency manifestations?



triggers?

A

neonatal jaundice -> kernicterus
acute hemolytic anemia

bite cells, hemighost cells, heinz bodies

when patient is well, blood film typically unremarkable


antimalarias - primaquine, dapsone

sulphonamides, ciprafloxacin, nitrofurantoin
vitamin K

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54
Q

pyruvate kinase deficiency blood film finding?

A

short projections on red blood cells (speculated red blood cells/echinocytes) -> increase after spleenectomy

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55
Q

pyrimidine 5 nucleotidase deficiency findings on blood film?

A

basophilic stippling

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56
Q

first line investigations for patient with unexplained hemolytic anemia?

A

dat test - detect immunoglobulins on rbcs/ exclude autoimmune hemolysis

urinary hemosiderin/hemoglobin - looking for evidence of intravascular hemolysis

osmotic fragility

G6PD +/- PK activity

electrophoresis -> hemoglobin causes

heinz body stain -> oxidative hemolysis eg G6PD, hemoglobin hammersmith

Hams test/flow cytometry -> paroxysmal nocturnal hemoglobinuria

thick and thin blood film - malaria

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57
Q

hemolytic anaemia management?

A

folic acid supplementation
avoid precipitants
red cell transfusion
immunisations against blood borne viruses -> hep A and hep B

cholecystectomy or spleenectomy if indicated

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58
Q

indications for spleenectomy?

A

transfusion dependence
growth delay
physical limitation hb < or equal to
hypersplenism which is symptomatic

not before 3 and aim to do before age 10 to not delay growth

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59
Q

give examples of situations in which you MUST order a blood film (allows for evaluation of rbcs, wbcs and platelets)

A

1. An unexpected life-threatening condition - malaria (parasites seen - also presents w thrombocytopenia, fever), babesiosis (intra and extracellular parasites seen, maltese cross shape seen, endemic to US, immunosuppressed RF), HIV positive and unwell - could be disseminated histoplasmosis.

2. ACUTE ANEAMIA- megaloblastic, paroxysmal cold hemoglobinuria(agglutination, spherocytes, erythrophagocytosis,), Hereditary spherocytosis (if reticulocyte is low, suggests parvovirus B19 infection). G6PD and hemaglobinuria

3. ITP and TTP (thrombotic thrombocytopenic purpura)

4. ACUTE LEUKEMIA

5. BURKITT LYMPHOMA (associated with AIDS)

6. ACUTE KIDNEY INJURY. could be due to:
- Multiple myeloma
- Haemolytic uraemic syndrome
- Thrombotic thrombocytopenic purpura
- Tumour lysis syndrome in high grade haematological neoplasms
- AML or lymphoma with hyperuricaemia

7. INFECTION-
malaria
dog bite (capnocytophaga canimorsis)
babesia
borrelia infection in north african child
(learn how these infections look on blood film)

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60
Q

if a patient with ITP and low platelets is given IVIG and later notes red urine, what is the likely cause?

A

hemoglobinuria - blood film may show spherocytes and polychromatic macrocytes suggesting hemolysis.
pathology = acute intravascular hemolysis resulting from antiA in IVIG, causing hemaglobinuria


rule out hematuria by centrifuging urine sample - if layers are formed/ separate to give a

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61
Q

always do a blood count and blood film with patient with new petechia or bruising.


what are some blood film explanations for thrombocytopenia?

A

Meningococcal sepsis - neutrophils will show basophilic inclusions of bacteria - MEDICAL EMERGENCY

thrombotic thrombocytopenic purpura - platelets not seen, fragmented rbcs!!!!!/shistyocytes - MEDICAL EMERGENCY - MAHA, thrombocytopenia, acute kidney injury, low ADAMTS13, headache abdominal pain due to thrombi.

HELLP Syndrome - MEDICAL EMERGENCY, deliver baby - blood film shows no platelets - MUST DO blood film as could be Malaria!

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62
Q

TTP management?

A

plasma exchange and corticosteroids
do not transfuse platelets - worsen condition

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63
Q

acute promyelocytic anemia
management

A

platelets and correction of hypofibrinogenaemia

immediate treatment with alltransretinoic even if diagnosis not confirmed

emergency
other causes of AML are less urgent unless there is leucostasis or SVC obstruction

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64
Q

when is acute lymphoblastic leukemia urgent?

A

when there is hyperleukocytosis
or SVC obstruction in T-ALL

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65
Q

macrocytic aneamia/folate deficiency + howell jolly bodies makes you think?

A

coeliac disease

spleenomegaly and damage -> howell jolly bodies

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66
Q

iron deficiency is what until proven otherwise?

A

bleeding (possibly cancer)

67
Q

leucoerythroblastic anemia features?

causes?

A

anemia with these on blood film:
- teardrop rbcs
- nucleated rbcs -should only be in bone marrow
- immature myeloid cells - should only be in bone marrow

caused by bone marrow infiltration:
1. malignancy - hematopoietic (eg leukemia) or non hematopoietic eg metastatic breast cancer
2. Myelofibrosis - Massive spleen!!!!(differentiates from other causes), dry tap on BM aspirate
3. severe infection - miliary tb, severe fungal infection

68
Q

immune hemolytic anemia features?

risk factors/causes?

A

spherocytes
+ve DAT test

cancer of immune system eg lymphoma, CLL
autoimmune - SLE
infection - mycoplasma
idiopathic

69
Q

acquired non immune hemolytic anemia causes

A

malaria

MAHA

70
Q

MAHA causes ?

blood film findings?

A

underlying adenocarcinoma
HUS

RBC fragments
thrombocytopenia

71
Q

what to ask when you see an abnormal wbc count?


state some causes of elevated wbc

A

is it all lineages or a particular one eg eosinophils?

are there cells in peripheral blood that shouldnt be found there? - eg myeloblast, myelocytes


- acute leukemia
- chronic myeloid leukemia
- Infectious mono - EBV, CMV, toxoplasma
- oesinophilia
- reactive neutrophilia - infection(toxic granules/vacuoles but no immature cells seen if infection vs CML which has neutophila +myelocytes and basophils), steroids, inflammation eg pancreatitis/myocarditis, underlying neoplasia

72
Q

causes of elevated LYMPHOCYTE count?



causes of reduced?

A

- Infectious mono - EBV, CMV, toxoplasma = atypical mature lymphocytes
- infectious hepatitis, rubella, herpes
- autoimmune disorders
- sarcoidosis
- CLL - small mature lymphocytes, smear cells
- ALL - immature/lymphoblasts

reduced:
- infection - HIV
- autoimmune
- inherited immune deficiency syndromes
- drugs - chemo

73
Q

how to distinguish monoclonal lymphocytosis (blood cancer) vs reactive lymphocytosis (infection) through immunophenotyping of B cells

A

Kappa and Lambda 60:40 = healthy bone marrow, reactive lymphocytosis

Kappa only or Lambda only 99:1 = leukemia or lymphoma

74
Q

female 39 with lymphoma stage 4 involving bone marrow, lymph nodes, liver

develops anemia, retciulocytosis, spherocyts

what could be the cause

A

could be anemia due to bone marrow inflitration - in this case would have low reticulocytes, DAT negative, if elevated biliuribin was conjugated will point away from hemolysis and towards liver mets. Leukoerythroblastic film will be seen

the answer is immune hemolytic anemia (cancer of immune system) - due to reticulocytosis and spherocytes not seen in bone marrow infiltration/leukoerythroblastic picture

75
Q

Diagnosis of hematological cancers method

A

morphology
immunophenotype - flow cytometry or immunohistochemistry
cytogenetics - chromosomal abnormalities
molecular genetics - DNA mutations

76
Q

what is lymphoma?

clinical presentation?



HL staging+values?

HL treatment?

A

cancer of lymphoid system/cells, typically of lymphatic system

bone marrow, thymus,(generative tissue) lymph nodes, spleen,(reactive tissue) blood

lymphadenopathy - cervical, axillary, mesenteric etc
spleenomegaly
compression of tubes-> ureter, bile duct, ivc etc
infiltration of organ-> eye, cns, liver failure
recurrent infection
constitutional symptoms - b symptoms, pruritus, alcohol induced painful lymphadenopathy

85% hodgkins

PET-CT scan
Ann Arbor stage:
stage 1 = single group of lymph nodes
stage 2 = >1 but on same side of diaphragm
stage 3 = nodes above and below diaphragm
stage 4 = extranodal spread -> bone marrow, liver (spleen does not count)

suffix A if none below, B if at least one
1. fever
2. night sweats
3. weight loss >10% in 6 months

(in a normal pet scan, the kidney, ureters, collecting duct and bladder light up as dye is excreted via this)

chemo
avoid radio due to risk of later cancer in tissues

77
Q

causes of non hodgkins lymphoma?

A

1. chronic antigenic stimulation - bacterial or autoimmune
- h pylori - gastric MALT
- sjogerens - MZL - marginal zone lymphoma
- hashimotos - MZL of thyroid
- coelaic disease - small intestine EATL enteropathy associated T cell lymphoma

2. Direct viral integration in lymphocytes
- HTLV 1

3. Loss of T cell function leading to increased risk of EBV associated B NHL
- HIV
- transplant immunosuppresion

78
Q

hodgkins lymphoma subtypes?

A

1. classical
2. lymphocyte predominant

79
Q

Non hodgkins lymphoma subtypes

differences from hodgkins?

A

1. B cell - most common
2. T cell

in NHL, neoplastic lymphoid cells can circulate in blood vs hodgkins involving 1 lymph node group and spreading contiguously to adjacent nodes

80
Q

Classification of common B cell NHLs

A

Low grade: (composed of small lymphocytes)
- Follicular lymphoma
- Small lymphocytic lymphoma/chronic - lymphocytic leukaemia
- Marginal zone lymphoma

High grade: (composed of large lymphocytes)
- Diffuse large B cell lymphoma
- Burkitt’s lymphoma

Aggressive:
- Mantle cell lymphoma

81
Q

follicular lymphoma features? - clinical?

chromosomal translocation? (Chromosomal translocations in lymphoma typically involve translocation of oncogene to fuse with immunoglobulin promoter -abnormal b cell development)

A

Clinical
- painless Lymphadenopathy MA/elderly

Molecular
14;18 IgH-Bcl-2 gene

82
Q

small lymphocytic lymphoma features

A

Clinical
MA/elderly; nodes/lymphadenopathy or blood

if little to no lymphadenopathy and high white cell count -> called CLL (composed of same cells)

83
Q

Marginal zone Lymphoma features

A

commonly arise in extranodal sites eg G/MALT lymphoma (responsive to antibiotics for Hpylori)

associated with inflammation - gastritis , sjogrens

84
Q

Mantle cell lymphoma features?

What molecule is expressed on histo pathology?

A

very aggressive
lymph nodes, GI tract
disseminated disease at presentation

histopathology - abberent CD5 and Cyclin D1 expression - D1 confirms diagnosis

t(11,14) IgH-CyclinD1

85
Q

Burkitt lymphoma features?

Chromosomal translocation?

A

Jaw or abdominal mass
typically children or young adults
EBV association

histopathology - starry sky appearance

IgH -C-myc

fastest proliferating malignancy

86
Q

Diffuse large B cell lymphoma features

A

MA/elderly, lymphadenopathy

histopathology - sheets of large lymphoid cells

87
Q

T cell lymphomas

A

lymphadenopathy and extranodal sites
large t lymphocytes

associated reactive cell populations especially eosinophils

examples:
- adult t cell lymphoma - associated with HTLV
- mycosis fungoides
- enteropathy associated t cell lymphoma - complication of ceoliac disease
- anaplastic large cell lymphoma - nucleoli are variable in appearance but prominent

88
Q

monitoring only is appropriate for asymptomatic small volume disease in which NHL subtype?

A

follicular lymphoma
- it is a low grade indolent lymphoma
- slow growing but not curable

*gastric malt is an exception for low grade lymphomas. it is indolent but you treat as it can be cured

89
Q

Hodgkins lymphoma subtypes?
which is most common in women and young?

features? staining markers?

A

nodular sclerosis - most common in women and young people
lymphocyte rich
lymphocyte depleted
mixed cellularity

reed-sternberg cells - bilobed nuclei
CD15, CD30 (2 owl eyes) - positive in classical HL, negative in nodular LP HL

90
Q

generally, lymphomas affect lymph nodes and leukemias affect blood

A

91
Q

CLL
pathology?
features including lab findings?
immunophenotype?

key prognostic factor?
clinical features?

management? - name a BCR kinase inhibitor and a BCL2 inhibitor

A

proliferation of mature B lymphocytes
disease of elderly - most common cause of lymphocytosis in elderly

lymphocytosis
smear cells
lymphocytic infiltration of bone marrow

immunophenotype:
- abberant B-CLL cells which express CD5 (should be negative)
- CD5+/CD19+

deletion of 17p (Tp53) greatly lowers survival
mutation of IgH V gene lowers survival

lymphadenopathy
bone marrow failure
infection succeptibilty -> loss of b cell antibodies
1% transform to lymphoma

- supportive: vaccinations but not live, antibiotics
- chemo
- targeted therapy - BCR kinase inhibitors(BTK/ibrutinib), BCL2 inhibitors (Venetoclax - risk of tumour lysis syndrome!!!)
- CAR-T therapy

92
Q

polycytheamia definition?
types?

A

raised HB and hematocrit concentrations

1. relative/pseudopolycythemia = lack of plasma (non-malignant)
2. True = excess erythrocytes, normal plasma vol.:
- secondary (non-malignant - increased EPO)
- primary myeloproliferative neoplasms (reduced EPO):
PV, ET, PMF (philadelphia chromosome negative)
CML (philadelphia chromosome positive)

93
Q

risk factors for pseudo-polycythemia?

A

alcohol, obesity, diuretics

94
Q

feature of secondary polycythemia?
causes?

A

raised EPO (EPO level important!! to rule out primary p.)

appropriately raised:
- high altitude
- hypoxic lung disease
- cyanotic heart disease
- high affinity hemoglobin

inappropriately raised:
- renal disease - cysts, tumours, inflammation
- uterine myoma
- other tumours (liver, lung)

95
Q

myeloproliferative neoplasms give rise to mature cells but just an increase in proliferation (many cells) vs acute leukemia with immature cells

myeloproliferative neoplasms may cause hepatomegaly or spleenomegaly

proliferation in these neoplasms often involve mutation in?

A

Tyrosin kinases eg JAK2, calreticulin

96
Q

Polcythemia vera
symptoms?

diagnosis

management?

A

- headaches, lightheadedness, TIA, stroke
- visual disturbances
- aquagenic pruritus

- FBC - raised HB and hematocrit
- genetic testing for JAK2
-(wcc and platelets may also be raised!)

reduce HCT
- venesecection, hydrocycarbamide
- keep platelets below normal range

97
Q

Essential thrombocythemia
symptoms?
diagnosis?
managment?

A

- incidental finding on fbc. raised platelets BUT wbc and rbcs/hb MUST be normal
- thrombosis, arterial or venous - strokes, TIA, PE, DVT
- bleeding - mucous membrane and cutaneous as platelets may be dysfunctional
- headaches, dizziness, visual disturbances

aspirin - prevent thrombosis
hydroxycarbamide
anagrelide - inhbits platelet formation

98
Q

Primary Myelofibrosis definition?
symptoms?
diagnosis?
managment?

A

malignant blood cells in bone marrow causing bone marrow fibrosis. thus symptoms:

- cytopenias!! - anemias, thrombocytopenias
- splenomegaly - may be MASSIVE (PMF and CML top of list for causes of massive spleen - eg spleen palpable in iliac fossa)
- hepatomegaly
(fibrotic bone marrow so hematopoeisis happening in liver and spleen)
- hypermetabolic state

blood film
- leucoerythroblastic film, tear drop cells

bone marrow
- dry tap

JAK2 mutation may be present


Jak2 inhbitor Ruxolotinib
Stem cell transplant

99
Q

CML
symptoms?
diagnosis?
management?

A

- thrombosis, monocular blindness
- bruising, bleeding
- hypermetabolism
- massive spleenomegaly -/- hepatomegaly (if lymphadenopathy as well would mean lymphoma instead most likely)

Fbc - leukocytosis
blood film - neutrophils, myelocytes NOT blasts, basophilia

t(9,22) translocation which creates BCR-ABL fusion gene/oncoprotein!!

*in advanced phase, it can transform to a blast crisis/AML

tyrosine kinase inhibitor -> imatinib -> white cell count expected to fall

100
Q

myelodysplastic syndromes classification?

features?

A

Must have:
1. cytopenia of at least on blood line. eg anemia
2. <20% blasts in blood or bone marrow but >5 (normal cut off). eg erythroblasts (can raise MCV)
3. morphological dysplasia of at least 10% in cell line OR molecular/genetic abnormalities

increased risk of transformation to acute myeloid leukemia - 1/3 OF people
disorders of the elderlybilobed neutrophils - Pelger Huet anomaly
abnormal granulation in neutrophils eg hypogranular
dysplastic rbcs and megakaryocytes

refractory anemia -> ringed sideroblasts (type of erythroblast). can also cause raised ferritin. if ferritin is too high, can cause liver failure etc -> treat at certain level

101
Q

MDS treatment?

A

blood product support
antimicrobial therapy - due to succeptibility to infection
biological modifiers eg immunosuppressive therapy

stem cell transplant
chemo

102
Q

primary causes of bone marrow failure

A

. PRIMARY
Congenital: Fanconi’s anaemia (multipotent stem cell)
Diamond-Blackfan anaemia (red cell progenitors)
Kostmann’s syndrome (neutrophil progenitors)
Acquired: Idiopathic aplastic anaemia (multipotent stem cell)

103
Q

secondary causes of bone marrow failure

A

Marrow infiltration:
Haematological (leukaemia, lymphoma, myelofibrosis)
Non-haematological (metastatic solid tumours, secondary fibrosis)
Radiation
Drugs
Chemicals (benzene)
Autoimmune
Infection (Parvovirus, Viral hepatitis, HIV)

104
Q

name drugs that can cause bone marrow failure

A

PREDICTABLE (dose-dependent, common)
Cytotoxic drugs

ANTIBIOTICS
Chloramphenicol
Sulphonamide

DIURETICS
Thiazides

ANTITHYROID DRUGS
Carbimazole

105
Q

Aplastic anemia causes?

presentation?

A

all age groups affected
mostly idiopathic

other causes:
Inherited: Dyskeratosis congenita (DC). Fanconi anaemia (FA), Shwachman-Diamond syndrome

secondary: drugs, radiation, infection

PNH

triad of anema, leukopenia, low platelets (bone marrow failure)
hypocellular bone marrow

106
Q

differentials for pancytopenia and hypocellular bonemarrow? (you dont need to memorise)

A

Aplastic anemia
Hypoplastic MDS / Acute Myeloid Leukaemia
Hypocellular Acute Lymphoblastic Leukaemia
Hairy Cell Leukaemia
Mycobacterial (usually atypical) infection
Anorexia Nervosa
Idiopathic Thrombocytopenic Purpura

107
Q

severe aplastic anemia criteria?

A

2 out of 3 peripheral blood features

1. Reticulocytes < 1% (<20 x 109/L)
2. Neutrophils < 0.5 x 109/L
3. Platelets < 20 x 109/L

Bone marrow <25% cellularity

108
Q

aplastic anemia treatment

A

blood products + iron chelation therapy
antimicrobials

immunosuppresive treatment - older patients
stem cell transplant - young
androgen treatment

109
Q

aplastic anemia complications

A

relapse

risk leukemia, mds, pnh, solid tumours

110
Q

cure rate for sibling related stem cell transplant for aplastic anemia in patients under 40?

A

70%

111
Q

Fanconi anemia

features?
complications?

A

most common genetic cause of aplastic anemia

Short Stature
Hypopigmented spots and café-au-lait spots
Abnormality of thumbs
Microcephaly or hydrocephaly
Hyogonadism
Developmental delay
No abnormalities 30%

AA, MDS, leukemia

112
Q

dyskeratosis congenita features?

genetic basis?

A

Marrow failure
Cancer predisposition
Somatic abnormalities

Patients may present with the Classical Triad of
Skin pigmentation
Nail dystrophy
Leukoplakia

telomere shortening (also seen in idiopathic AA) -> bone marrow failure

113
Q

women with facial plethora, high platelets, high neutrophils, high Hb,

what is a likely cause?

A

polycythemia vera

- high rbc count is not feature of cml

tests:
- analysis for JAK2 mutation
- bone marrow aspiration and trephine biopsy
- serum erythropoeitin

may do tests to exclude secondary polycythemia eg CXR if smoker

114
Q

extensive atheromatous disease, diabetes mellitus

post abdominal aortic aneurysm repair:
presenting with acute renal impairment, sepsis, respiratory distress

blood film:
toxic granualation and vacuolation
left shit
rouleaux

most likley cause of high wcc?

A

reactive neutrophilia

115
Q

64 year old woman with splenomegaly

leucocytosis with myelocytes and basophilia

most likely diagnosis?

A

chronic myeloid leukemia

its NOT acute myeloid leukemia because platelet count is normal

116
Q

man with bruising with isolated low platelets? week later, neutrophils, rbcs still normal. most likely diagnosis

A

ITP

117
Q

baby/ neonate with brusies, differentials?

A

non accidental injury
coagulation abnormality
thrombocytopenia

118
Q

woman with 18 month old baby

microcytic hypochromic anemia some anisocytosis, some elongated rbcs

questions to ask?

a differential?

A

bleeding - especially menstrual bleeding
history of pregnancies
diet


IDA

119
Q

differentiating osteomyelitis and septic arthritis in kids

A

osteomyelitis will show bone changes vs septic arthritis wont

osteomyletis more common in kids

120
Q

causes of polycythemia in neonates?

A

twin to twin transfusion
intrauterine hypoxia
placental insufficiency

121
Q

learn about hemoglobinopathies and thalessemias in children, learn about hemolytic anemias

A

122
Q

why is sickle cell different in child vs adult?

A

red marrow that in childhood that can be infarcted

123
Q

B12 diagnosis signs

A

hypersegmented neutrophils - blood film
giant metamyloctes - bone marrow

124
Q

how does autologous transplantation work?

USED IN?

A

growth factor infusion -> collect stem cells in remission -> thaw and reinfuse and give high dose chemo

used in:
- acute leukemia, myeloma, lymphoma, CLL
- solid tumours - germ cell tumours
- autoimmune diseases - Scleroderma, MS

125
Q

how does allogenic transplantation work?

A

high dose chemo and radio -> infuse bone marrow or stem cells from HLA matched donor


used for:
all blood cancers
bone marrow failure - eg aplastic anemia
congenital immune deficiencies

126
Q

how do you gain hematopoeitic stem cells?

A

1. Bone marrow
2. peripheral blood
give g-scf -> cells circulate in blood stream -> harvest peripheral blood

3. umbilical cord

127
Q

Graft vs host disease
symptoms?
treatment?
strongest prognostic factor?

A

acute = skin, GI tract (nausea -> bloody diarrhea), liver

chronic = skin, mucous membranes, lungs liver eyes joint, immune dysregulation, immune dysfunction

worry of gram -ve infections
corticosteroids etc

prior acute gVHD = strongest prognostic factor

128
Q

risk factors for GVHD?

A

conditioning regimen - if it causes a lot of cell death/toxicity will increase GVHD

sex mismatch
with PBSC worse than bone marrow

if patient has concomitant viral infection

higher HLA mismatch

recipient age and disease phase

129
Q

Methods to prevent Acute GVHD?

A

methotrexate
corticosteroids
calcineurien inhibitors (cyclosporin A, tacrolimus, sirolimus)
CsA + MTX

(donor) T cell depletion!!!
post-transplant cyclophosphamide

130
Q

onset timeline of infections post transplant

A

bacteria - early onset. gram +ve typically from vascular access. gram -ve from GI tract and are much more dangerous!!/cause most deaths eg ecoli
viruses - tend to come later except herpes simplex = early

131
Q

post stem cell transplant bugs

A

CMV - pnuemonitis, retinitis etc. more common in seropositive than seronegative people
EBV
resp viruses
BK and hemorrhagic cystitis
adenovirus

132
Q

changes to fbc during pregnancy?

A

1. thrombocytopenia - and increased platelet size
2. mild anemia - red cell mass increases but plasma volume more
3. macrocytosis - phyisiological but also due to folate/b12 deficiency
4. neutrophilia

133
Q

impacts of iron deficiency during pregnancy?

A

IUGR, prematurity, ppH

134
Q

define anemia in pregnancy

A

HB <110 in 1st trimester
and <105 in second and 3rd

135
Q

causes of thrombocytopenia in pregnancy?

A

physiological/gestational thrombocytopenia = most common. lower platelet count, less likely to be

preeclampsia

ITP

microangiopathic syndromes - deposition of platelets in blood vessels. platelets shear rbcs - hellp, ttp, pet, hus, aflp, sle, etc

other things that could also happen when non pregnant: bone marrow failure, leukemia etc

136
Q

ITP treatment in pregnancy?

A

IV immunoglobulin
steroids

137
Q

coagulation changes in pregnancy?

A

increase in procoagulant factors and decrease in anticoagulants eg protein S

138
Q

VTE highest risk time during pregnancy?

risk factors for VTE

investigations

DVT is more common on which leg?



how to treat women with risk f actors for VTE?

A

6 weeks post partum period

BMI!!!, hyperemesis gravidarum, preeclampsia, operative delivery, previous thromboisis/fh, age >35, parity, multiple pregnancy, ovarian hyperstimulation syndromes eg from drugs given in IVF, medical problems eg HBSS, nephrotic syndrome


Doppler, VQ
ddimer not useful as elevated in pregnancy

left dvt

prophylactic LMWH, Mobilise early, maintain hydration. Stop LMWH For labour, epidural, delivery

139
Q

condition caused by warfarin use during pregnancy?

A

chondrodysplasia punctata

140
Q

causes of pospartum hemorrhage?

A

4Ts

Tone = Uterine aTony!
Trauma = Laceration/Uterine rupture!
Tissue = Retained placenta
Thrombin - coagulopathy = DIC in abruption or amniotic fluid embolism. dilutional coagulopathy after resus

141
Q

causes of DIC?

A

amniotic fluid embolism
abrupt placenta
retained dead fetus
severe preclampsia
sepsis
(they all cause exposure of tissue factor)

+ coagulation changes in pregnancy is a cause

142
Q

amniotic fluid embolism presentation?

A

sudden onset shivers, vomiting, shock, DIC

(tissue factor in amniotic fluid)

143
Q

how to differentiate IDA from thalassemia trait

A

IDA = Low HB, low or normal RBC

Thalassemia trait = normal HB, increased RBC
- increased HBA2 in b thal trait
- normal in alpha thal trait

144
Q

Multiple myeloma features

risk factors

symptoms

complications?

imaging?

A

bence jones protein in urine
serum IgG or IgA - paraprotein or m spike
monoclonal kappa or lambda serum free light chains

age - median = 67
genetics - black
obesity
men> women

crab
hypercalcemia
renal disease
anemia
bone disease

immunosuppresion and infections

AL amyloidsois - renal(due to serum free light chains deposits) , heart failure, cord compression, hypercalcemia

FDG-PET

145
Q

Diagnostic criteria for MGUS?

risk factors for progression to MM?

A

1. <10% plasma cells
2. Monoclonal protein spike <30 g/L
3. no CRAB symptoms or organ damage
* No evidence of other B-cell proliferative disorder

146
Q

Diagnostic criteria for smouldering myeloma?

A

1. >10% plasma clone cells
2. +/- M spike (monoclonal protein spike) >/= 30
3. no organ damage or CRAB symptoms!! vs multiple myeloma


MGUS -> smouldering myeloma > myeloma
no paraprotein in serum or urine

147
Q

what two conditions preceed multiple myeloma?

A

MGUS and smouldering myeloma

148
Q

AL amyloidosis symptoms?

A

nephrotic syndrome
HF
sensory neuropathy
abnormal LFTS
macroglossia

149
Q

name a feature of high risk multiple myeloma

A

t(4,14) IGH/FGFR3 and del17p in TP53

150
Q

median survival of people diagnosed with myeloma today?

A

151
Q

list two causes of
microcytic anemia
normocytic anemia
macrocytic aneamia

A

152
Q

what are the b cell markers?
T cell markers?

what is TDT a marker of? what does it suggest?
what is surface Ig a marker of?

A

B = CD19 and 20

T = CD3, CD4, CD8, CD5

TDT = marker immature B and T lymphoblasts. always suggestive of ALL

Surface Ig = mature B cells and plasma cells

153
Q

36 year old woman, fatigue, joint pains with malr rash, menorrhagia, ESR 80. Bloods show low hb, raised LDH, bilirubin, reticulocytes. blood film shows rbcs with no central pallor. most likely diagnosis

A

hemolytic anemia -> spherocytocsis

autoimune spherocytosis - Dat +ve
inherited spherocytosis - Dat -ve

154
Q

learn about hemolytic anemias, both inherited and acquired

A

155
Q

Give two examples of a DAT -ve acquired hemolytic anemia. (non immune)

A

hypersplenism, malaria, MAHA

156
Q

low ferritin confirms what condition?

normal or high ferritin means what?

What happens to transferrin/transferrin saturation in IDA and ACD?

A

IDA

may be IDA or ACD

high in IDA
low/normal in ACD

157
Q

name some non malignant causes of pancytopenia

A

1. B12 Deficiency/folate. anemia will be macrocytic
2. aplastic anemia

158
Q

pancytopenia + tear drop cells on blood film points to?

A

myelofibrosis

159
Q

healthy 58 year old man. routine fbc -> high wcc with high neutrophils. blood film shows excess basophils and myelocyte presence and neutrophils. everything else normal.

what is the single most useful test to confirm diagnosis?

A

BCR ABL 1 PCR assay - for t(9,22)

- CML = most likely diagnosis

*Hb are typically well preserved or raised in CML

160
Q

treatment for CML?

A

tyrosine kinase inhibitor

161
Q

What mutation is commonly tested for in CLL?

CLL symptoms
what can it progess into

treatments?

A

TP53 mutation status - more aggressive disease with mutation

Proliferation of mature non functional b cells. can cause lymphadenopathy and spleenomrgally. increased risk of infection due to hypgammaglobulinemia

lymphoma = richter transformation

BCR kinase inhibitors - ibrutinib
bcl2 inhibitors - venetoclax

162
Q

which factors carry the highest risk of thrombosis?

A

antithrombin deficiency
family history of thrombosis

163
Q

risk of recurrence is highest after what type of thrombotic event?

A

idiopathic - long term anticoagulation

COCP, flights trauma -> minor precipitants -> 3 months anticoagulation

- no need for long term anticoagulation after surgery

Year 5 MEDICINE Pathology (11 decks)

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